In vitro and in vivo antiviral activity of Maqian (Zanthoxylum myriacanthum var. pubescens) essential oil and its major constituents against strains of influenza virus
In vitro and in vivo antiviral activity of Maqian (Zanthoxylum myriacanthum var. pubescens) essential oil and its major constituents against strains of influenza virus
复制标题
马千精油及其主要成分对流感病毒株的体内外抗病毒活性
DOI：
10.1016/j.indcrop.2022.114524
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发表时间：
2022-01-08
影响因子：
5.9
通讯作者：
Li，Song
中科院分区：
文献类型：
--
作者：
Yang，Jingjing;Zhao，Lei;Li，Song
毛花椒（Zanthoxylummyriacanthumvar.pubescens，简称“麻前”）是我国西南少数民族广泛食用的一种经济植物。近年来，麻钱挥发油的抗炎等药理作用日益受到重视。本研究对麻钱挥发油及其主要成分d/L-柠檬烯的体外和体内抗流感病毒活性进行了评价。在体外实验中，马钱挥发油和d/L-柠檬烯对甲型流感病毒和B型流感病毒均有较好的抗病毒作用。结果表明，麻钱挥发油对耐药流感病毒株有较强的抑制作用，EC 50为1.87 ± 1.04 μg/ml，选择指数为85.13。作用方式分析表明，麻钱精油和d/L-柠檬烯在细胞内复制阶段抑制流感病毒。对于体内治疗效果，d/L-柠檬烯的灌胃和鼻内给药保护超过50%的小鼠免受致命的流感病毒攻击。与病毒组相比，感染性病毒颗粒和病毒基因组RNA在IL-柠檬烯处理的小鼠中减少约2倍。d/L-柠檬烯治疗有效地改善了流感病毒感染小鼠的病理特征。基因表达水平分析显示，经柠檬烯处理的小鼠肺组织中主要的促炎细胞因子IL-1β、IL-6和TNF-α均显著降低。有趣的是，我们发现D-柠檬烯在抑制促炎细胞因子方面比L-柠檬烯更有效。转录组分析显示，32个宿主基因参与了抗病毒过程，其中大部分与免疫系统和信号转导有关。结合柠檬烯的抗病毒和免疫调节作用，我们认为这种多功能单萜有潜力成为一种新的抗流感病毒感染的候选药物。
Zanthoxylummyriacanthumvar.pubescens(Maqian) is an economically important plant that is widely consumed as a flavoring agent or indigenous medicine by local ethnic groups in Southwest China. The pharmacological activities, such as the anti-inflammatory activity of Maqian essential oil, have been highlighted in recent years. In this study, thein vitroandin vivoanti-influenza activities of Maqian essential oil and its major ingredient,d/L-limonene, were assessed. The Maqian essential oil andd/L-limonene were effective against the influenza A and influenza B virusesin vitro. Notably, the Maqian essential oil was highly inhibitive against the drug-resistant influenza virus strain with an EC50of 1.87 ± 1.04 μg/ml and a selective index of 85.13. Mode-of-action analysis revealed that Maqian essential oil andd/L-limonene inhibited the influenza virus at the stage of intracellular replication. Forin vivotherapeutic efficacy, both intragastric and intranasal administration ofd/L-limonene protected over 50% of mice from lethal influenza virus challenge. Both infectious viral particles and viral genome RNA were decreased approximately 2-fold in thed/L-limonene-treated mice compared with the virus group. Treatment withd/L-limonene potently improved the pathological features of the influenza virus-infected mice. Analysis of the gene expression level revealed that the major proinflammatory cytokines, including IL-1β, IL-6 and TNF-α, were significantly decreased in thed/L-limonene treated mouse lung tissues. Interestingly, we found thatD-limonene was more potent thanL-limonene in inhibiting proinflammatory cytokines. Transcriptome analysis revealed 32 host genes that participated in the antiviral process, most of which were related to the immune system and signal transduction. Combined with the antiviral and immunoregulatory effects of limonene, we believe that this multi-functional monoterpene has potential to become a novel candidate against influenza virus infections.